The Antibiotic Rifampin to Reduce High Levels of Blood and Urine Calcium in IIH

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Idiopathic infantile hypercalcemia(IIH) is a rare,genetic disorder of mineral metabolism. Biallelic loss of functions mutations of CYP24A1, the gene encoding the 24-hydroxylase enzyme that represents the principal pathway for inactivation of vitamin D metabolites, cause the most common and severe form of IIH.Investigators have preliminary data supporting a novel therapeutic approach to suggest rifampin as an investigational drug to induce over-expression of CYP3A4, an important enzyme that provides an alternate catabolic pathway for inactivation of vitamin D metabolites. In this study, investigators will recruit 5 patients with biallelic inactivating mutations of CYP24A1. Participants will be followed prospectively for a total 6-11 months. This will include 2 months of observation, 2 months of receiving the starting dose of rifampin, followed by 2 month washout phase. Efficacy of the starting dose of rifampin will be determined prior to proceeding only in non responders to the escalation dose of rifampin 10mg/kg/day.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Hospital for Sick Children
• Collaborators: Canadian Institutes of Health Research (CIHR); Children's Hospital of Philadelphia; Cures Within Reach
• Treatments: Rifampin

Criteria

Inclusion Criteria:

• all patients between 6 months- 17 years of age with the clinical phenotype of idiopathic infantile hypercalcemia

• Biochemical evidence of this disorder: Serum calcium>upper limit of the reference age for range; high, 1,25 (OH)D; reduced PTH, reduced 24,25(OH)2D, and suppresses 24,1,25 (OH)2D, normal serum creatinine, AST, and ALT with or without

• biallelic inactivating mutations of CYP24A1

• mutations in newly published genes which are shown during the course of the study to cause an inappropriate increase in 1,25 (OH)2D

Exclusion Criteria:

• Allergy to rifampin or related medications

• Pregnancy or breastfeeding

• Significant cardiac, hepatic, or endocrine comorbidities

• Taking any medications/foods known to interact with CYP3A4 or 1,25 (OH)D

• Parents or guardians or subjects who in the opinion of the Investigator may be non compliant with study schedules or procedures

• Other comorbidities considered unsuitable by the investigator, including TB